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| Open AccessPeptide-oligourea hybrids analogue of GLP-1 with improved action in vivo
The peptide hormone GLP-1 has the potential to be a remedy for diabetes type II, yet is unstable. Here, the authors synthesized α-peptide-oligourea hybrid analogues of GLP-1 some of which showing significantly prolonged activity in vivo.
- Juliette Fremaux
- , Claire Venin
- & Sébastien R. Goudreau
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Article
| Open AccessDinitroimidazoles as bifunctional bioconjugation reagents for protein functionalization and peptide macrocyclization
The selective formation of protein bioconjugates under physiological conditions is a challenging task. Here, the authors report that 1,4-dinitroimidazoles are reagents of choice for protein bioconjugation at either cysteine or lysine sites within short times and provide facile access to peptide macrocycles.
- Qunfeng Luo
- , Youqi Tao
- & Huan Wang
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Article
| Open AccessLithium hexamethyldisilazide initiated superfast ring opening polymerization of alpha-amino acid N-carboxyanhydrides
Ring-opening polymerizations of α-amino acid N-carboxyanhydrides to form polypeptides are usually sensitive to moisture, slow and can undergo side reactions. Here the authors use lithium hexamethyldisilazide to initiate α-amino acid N-carboxyanhydride polymerizations that is very fast and can be conducted in an open vessel.
- Yueming Wu
- , Danfeng Zhang
- & Runhui Liu
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Article
| Open AccessDesign of Peptoid-peptide Macrocycles to Inhibit the β-catenin TCF Interaction in Prostate Cancer
Small molecules and peptide inhibitors have their benefits and faults when it comes to inhibiting protein-protein interactions. Here, the authors designed a peptoid-peptide hybrid that inhibited β-catenin/TCF interactions, leading to inhibition of Wnt signalling in models of prostate cancer.
- Jeffrey A. Schneider
- , Timothy W. Craven
- & Susan K. Logan
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Article
| Open AccessPeptide-guided functionalization and macrocyclization of bioactive peptidosulfonamides by Pd(II)-catalyzed late-stage C–H activation
Aryl sulfonamides and sultams are important pharmacophores in medicinal chemistry. Here, the authors report a practical palladium-catalyzed C–H activation assisted by amino-acid residues in the substrate leading to arylsulfonamides and bioactive peptidosulfonamide macrocycles.
- Jian Tang
- , Hongfei Chen
- & Huan Wang
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Article
| Open AccessQuantum confined peptide assemblies with tunable visible to near-infrared spectral range
Quantum confined (QC) materials have favorable photoluminescent properties, yet are less bioavailable. Here, the authors developed aromatic cyclo-dipeptides that assemble into quantum dots and organize into biocompatible QC supramolecular structures suitable for in vivo imaging and optoelectronics.
- Kai Tao
- , Zhen Fan
- & Junbai Li
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Article
| Open AccessPalladium prompted on-demand cysteine chemistry for the synthesis of challenging and uniquely modified proteins
Cysteine side chains are reactive sites of protein synthesis and modification. Here, the authors show that tuning palladium chemoselectivity allows for selective removal of several cysteine protection groups, and use their method to synthesize challenging protein analogues.
- Muhammad Jbara
- , Shay Laps
- & Ashraf Brik
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Article
| Open AccessMolecular basis for the production of cyclic peptides by plant asparaginyl endopeptidases
Asparaginyl endopeptidases (AEPs) are plant proteases that can also function as ligases, catalyzing the production of cyclic plant peptides. Here, the authors identify structural features that govern AEP ligase activity, providing insights to aid the discovery and engineering of ligase-type AEPs.
- M. A. Jackson
- , E. K. Gilding
- & D. J. Craik
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Article
| Open AccessIdentification of single amino acid differences in uniformly charged homopolymeric peptides with aerolysin nanopore
Existing methods used for peptide analysis suffer from low sensitivity and specificity. Here the authors demonstrate the nanopore-based size-discrimination and purity analysis of short homopolymeric peptides with a single amino acid resolution.
- Fabien Piguet
- , Hadjer Ouldali
- & Abdelghani Oukhaled
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Article
| Open AccessElectric fields control the orientation of peptides irreversibly immobilized on radical-functionalized surfaces
Implanted materials can be rejected by the body, and coating the surfaces with peptides is seen as an option to overcome this problem. Here, the authors investigated how pH and electric fields can be used to prepare defined peptide coatings.
- Lewis J. Martin
- , Behnam Akhavan
- & Marcela M. M. Bilek
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Article
| Open AccessA prebiotic template-directed peptide synthesis based on amyloids
Amyloids may have played an important role in prebiotic molecular evolution but understanding replication of such information-coding molecules is still a problem. Here the authors design a model amyloid substrate and demonstrate sequence regio- and stereoselectivity during template-based replication.
- Saroj K. Rout
- , Michael P. Friedmann
- & Jason Greenwald
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Article
| Open AccessPhage display and selection of lanthipeptides on the carboxy-terminus of the gene-3 minor coat protein
Lanthipeptides are a class of cyclic post-translationally modified peptides with potential drug-like properties. Here the authors develop a phage display system by expressing lanthipeptide precursors as C-terminal fusions to the phage M13 coat protein pIII in E. coli along with the heterologous modifying enzymes.
- Johannes H. Urban
- , Markus A. Moosmeier
- & Josef Prassler
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Article
| Open AccessAntimicrobial peptides in frog poisons constitute a molecular toxin delivery system against predators
To avoid being eaten, poisonous prey animals must rely on fast passage of toxins across a predator’s oral tissue, a major barrier to large molecules. Here, Raaymakers et al. show that antimicrobial peptides co secreted with frog toxins enhance intoxication of a snake predator by permeabilizing oral cell layers.
- Constantijn Raaymakers
- , Elin Verbrugghe
- & Kim Roelants
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Article
| Open AccessSelf-assembling dipeptide antibacterial nanostructures with membrane disrupting activity
Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, but their antibacterial properties can be overlooked. Here the authors show the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers.
- Lee Schnaider
- , Sayanti Brahmachari
- & Ehud Gazit
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Article
| Open AccessCompetition between crystal and fibril formation in molecular mutations of amyloidogenic peptides
Aggregation of amyloidogenic peptides into fibrils and crystals has incidence in several amyloid-related diseases. Here, the authors investigate the origins of the fibril-to-crystal conversion in amyloidogenic hexapeptides pointing to the amyloid crystals as the ground state in the protein folding energy landscape.
- Nicholas P. Reynolds
- , Jozef Adamcik
- & Raffaele Mezzenga
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Article
| Open AccessContinual reproduction of self-assembling oligotriazole peptide nanomaterials
Molecules that act as both autocatalysts and material precursors offer exciting prospects for self-synthesizing materials. Here, the authors design a triazole peptide that self-replicates and then self-assembles into nanostructures, coupling autocatalytic and assembly pathways to realize a reproducing supramolecular system.
- Roberto J. Brea
- & Neal K. Devaraj
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Article
| Open AccessModulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands
Hydrogen bonding plays a major role in determining the tridimensional structure of biopolymers. Here, the authors show that control over a polypeptide conformation can be achieved by altering the donor-acceptor properties of side-chain triazole units via protonation-deprotonation.
- Ziyuan Song
- , Rachael A. Mansbach
- & Jianjun Cheng
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Article
| Open AccessAcylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides
A major challenge for the application of peptide therapeutics is their short half-lifein vivo. Here, the authors design peptide-fatty acid chimeras bearing an engineered linker that promotes albumin binding and allows longer circulation times of therapeutic peptides in animal models.
- Alessandro Zorzi
- , Simon J. Middendorp
- & Christian Heinis
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Article
| Open AccessRationally designed mineralization for selective recovery of the rare earth elements
Lanthanide elements are difficult to separate from aqueous solution with low energy input. Here, the authors design a peptide that recognizes and drives the precipitation of an insoluble lanthanide complex under physiological conditions, introducing a biomineralization-based approach for rare earth recovery.
- Takaaki Hatanaka
- , Akimasa Matsugami
- & Nobuhiro Ishida
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Review Article
| Open AccessExploring chemoselective S-to-N acyl transfer reactions in synthesis and chemical biology
The conversion of thioesters to amides via acyl transfer has become one of the most important synthetic techniques for the chemical synthesis and modification of proteins. This review discusses this S-to-N acyl transfer process, and highlights some of the key applications across chemistry and biology.
- Helen M. Burke
- , Lauren McSweeney
- & Eoin M. Scanlan
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Article
| Open AccessHighly selective inhibition of histone demethylases by de novo macrocyclic peptides
JmjC histone demethylases (KDMs) are cancer targets due to their links to cell proliferation, but selective inhibition remains a challenge. Here the authors identify potent inhibitors of KDM4A-C—viain vitroselection from a vast library of cyclic peptides—that show selectivity over other KDMs.
- Akane Kawamura
- , Martin Münzel
- & Christopher J. Schofield
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Article
| Open AccessSequence-selective encapsulation and protection of long peptides by a self-assembled FeII8L6 cubic cage
One of the challenges of synthetic self-assembled capsules is achieving selective recognition of specific cargoes. Here, authors synthesize a self-assembled porphyrin cubic cage that is capable of sequestering imidazole and thiazole-containing small molecules and peptides, protecting them from proteolysis.
- Jesús Mosquera
- , Bartosz Szyszko
- & Jonathan R. Nitschke
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Article
| Open AccessA minimal length rigid helical peptide motif allows rational design of modular surfactants
Emulsifiers are used in the pharmaceutical, food, cosmetic, and biomedical industry. Here the authors fabricate rigid helical peptides that can perform as emulsifiers and thickeners, which typically requires synergistic effects of surfactants and polysaccharides.
- Sudipta Mondal
- , Maxim Varenik
- & Ehud Gazit
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Article
| Open AccessTotal synthesis of feglymycin based on a linear/convergent hybrid approach using micro-flow amide bond formation
Feglymycin is a biologically active peptide but a challenging synthetic target due to the highly racemizable nature of the 3,5-dihydroxyphenylglycine groups. Here the authors report the synthesis of feglymycin using a microflow system, allowing amide bond formation without severe racemization.
- Shinichiro Fuse
- , Yuto Mifune
- & Hiroshi Tanaka
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Article
| Open AccessSpontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide
Antimicrobial peptides (AMPs) selectively form pores in microbial membranes in process not fully understood. Here the authors use experimentally guided molecular dynamics to study maculatin pore formation, showing how this AMP assembles into transient and structurally diverse oligomeric pores in cell membranes.
- Yukun Wang
- , Charles H. Chen
- & Jakob P. Ulmschneider
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Article
| Open AccessPACAP suppresses dry eye signs by stimulating tear secretion
Dry eye disease is a complex condition with limited treatments. Here the authors show that mice lacking a multi-functional peptide PACAP develop dry eye-like signs that can be topically treated with PACAP peptide that stimulates tearing in mice, suggesting a possible therapy in humans with dry eyes.
- Tomoya Nakamachi
- , Hirokazu Ohtaki
- & Seiji Shioda
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Article
| Open AccessHigh-flexibility combinatorial peptide synthesis with laser-based transfer of monomers in solid matrix material
Peptide arrays are used in areas such as measuring protein-protein interactions, but achieving high density in synthesis is challenging. Here, the authors report a method for the combinatorial synthesis of high density peptides arrays by laser driven sequential transfer of monomers onto acceptor surfaces.
- Felix F. Loeffler
- , Tobias C. Foertsch
- & Alexander Nesterov-Mueller
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Article
| Open AccessAnalytic framework for peptidomics applied to large-scale neuropeptide identification
Neuropeptide research is challenged by technical difficulties in identifying new bioactive peptides. Here the authors present an analytical pipeline for large-scale peptidomics applied to the rat hypothalamus, identifying thousands of endogenous neuropeptides and their post-translational modifications.
- Anna Secher
- , Christian D. Kelstrup
- & Jesper V. Olsen
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Article
| Open AccessSpacer-free BODIPY fluorogens in antimicrobial peptides for direct imaging of fungal infection in human tissue
Functionalizing antimicrobial peptides with fluorescent groups is a useful strategy for imaging infection, but the tag can alter the performance of the probe. Here, the authors report a spacer-free method to directly functionalise an amino acid with a fluorogenic group and prepare peptide-based imaging agents for fungal infection.
- Lorena Mendive-Tapia
- , Can Zhao
- & Marc Vendrell
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Article
| Open AccessEndothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells
Understanding coronary vessels development provides basis for regenerative strategies. Here, Soh et al. identify endothelin-1 as a key molecule driving long-term expansion of ISL1+bipotent vascular progenitors derived from human embryonic stem cells, and show that these cells can regenerate coronary vessels in mice.
- Boon-Seng Soh
- , Shi-Yan Ng
- & Kenneth R. Chien
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Article
| Open AccessIncreased amyloidogenic APP processing in APOE ɛ4-negative individuals with cerebral β-amyloidosis
Autosomal dominant Alzheimer's disease is thought to be caused by increased amyloidogenic APP processing. Mattson et al.show that association between brain Aβ and cerobrospinal fluid Aβ40 levels is stronger in APOE ɛ4 negative people, suggesting that increased processing may also underlie sporadic disease.
- Niklas Mattsson
- , Philip S. Insel
- & Oskar Hansson
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Article
| Open AccessCold denaturation induces inversion of dipole and spin transfer in chiral peptide monolayers
Spin selectivity for electron transport through peptide monolayers depends on the dipole moment of the system. Here, the authors show that self-assembled monolayers of peptides with α-helix structures transform to more linear structures upon cooling, inducing a flip in the direction of dipole moment and a change in preferred spin for electron transport.
- Meital Eckshtain-Levi
- , Eyal Capua
- & Ron Naaman
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Article
| Open AccessDiscovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway
Pathogenic microbes can often attach to surfaces and form biofilms that display increased antibiotic resistance. Here, the authors characterize the biosynthesis of a new class of natural products, the cahuitamycins, that inhibit formation of biofilms by the pathogenic bacterium Acinetobacter baumannii.
- Sung Ryeol Park
- , Ashootosh Tripathi
- & David H. Sherman
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Article
| Open AccessEfficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase
Cyclotides are plant backbone-cyclised peptides with potential as pharmaceutical scaffolds. Here the authors report on the efficient backbone cyclization of cyclotides and unrelated peptides by a newly identified asparaginyl endopeptidase from Oldenlandia affinis.
- Karen S. Harris
- , Thomas Durek
- & Marilyn A. Anderson
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Article
| Open AccessFormation of oligopeptides in high yield under simple programmable conditions
Typically, in order to form large peptides, complex procedures or activating agents are required. Here, the authors show that simple aqueous conditions with dehydration-hydration cycles are sufficient for the oligomerization of amino acids into peptides (up to 20 amino acids long) in yields of up to 50%.
- Marc Rodriguez-Garcia
- , Andrew J. Surman
- & Leroy Cronin
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Article
| Open AccessResidue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance
The pH-low insertion peptides (pHLIPs) respond to environmental pH variations by forming transmembrane α-helices. Here, the authors present the residue-specific structures and membrane locations of pHLIPs at different pH levels to probe the mechanism of their pH-dependant membrane insertion.
- Nicolas S. Shu
- , Michael S. Chung
- & Wei Qiang
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Article |
MARQUIS: A multiplex method for absolute quantification of peptides and posttranslational modifications
The absolute quantification of proteins and level of modifications between biological samples remain fraught with technical difficulties. Here, the authors present MARQUIS, a new mass spectrometry method that allows for precise absolute quantification of posttranslational modifications in complex protein samples.
- Timothy G. Curran
- , Yi Zhang
- & Forest M. White
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Article |
A peptide derived from laminin-γ3 reversibly impairs spermatogenesis in rats
The temporal opening and closing of cell–cell junctions at the blood–testis barrier allows the passage of immature germ cells during spermatogenesis. Su and colleagues identify a peptide fragment of the laminin-γ3 chain that disrupts the blood–testis barrier and reversibly impairs spermatogenesis in rats.
- Linlin Su
- , Dolores D. Mruk
- & C. Yan Cheng
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Article
| Open AccessBackbone rigidity and static presentation of guanidinium groups increases cellular uptake of arginine-rich cell-penetrating peptides
Cell-penetrating peptides can deliver molecular cargoes into living cells, and cross biological membranes by transduction—a non-endocytic mechanism. Here, the transduction efficiency of cyclic arginine-rich peptides is shown to be higher than that of more flexible linear peptides.
- Gisela Lättig-Tünnemann
- , Manuel Prinz
- & M. Cristina Cardoso